The objectives of the program are to contribute to a greater understanding of mechanisms involved in the hemostatic process and to relate this information to the pathophysiology of thromboembolic and hemorrhagic diseases. Information to be obtained relates to the following areas: the structure of adult and "fetal" fibrinogen and their catabolites, mechanism of fibrin polymerization, factors controlling fibrinogen synthesis and assembly, pathways of fibrinogen metabolism, mechanism of thrombin action, structure and metabolism of factor XIII of plasma and platelets, structure and function of the 'Cold-Insoluble Globulin' of plasma, and the relationship of platelet metabolism to platelet hemostatic functions; studies of the structure and mechanism of polymerization of the clotting protein of Limulus Polyphemus' (Horseshoe Crab) amebocytes will also be carried out - these investigations will be correlated with those proposed for mammalian clotting protein (i.e., fibrinogen). These problems are to be explored and analyzed by a comprehensive variety of biophysical, biochemical and immunochemical techniques. These types of analyses will be combined with tissue culture techniques in carrying out certain of the Program goals.